The GTP-binding release factor eRF3 as a key mediator coupling translation termination to mRNA decay
The GTP-binding release factor eRF3 as a key mediator coupling translation termination to mRNA decay
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DOI：
10.1074/jbc.m405163200
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发表时间：
2004-10-29
影响因子：
4.8
通讯作者：
Katada, T
中科院分区：
文献类型：
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作者：
Kobayashi, T;Funakoshi, Y;Katada, T
GTP是真核生物翻译终止所必需的，释放因子3(ERF3)与eRF1形成复合体，是鸟嘌呤核苷酸结合蛋白。此外，eRF3调节末端偶联事件，eRF3与聚(A)结合蛋白(Pab1)和监视因子UPF1相互作用，介导正常和无义介导的mRNA衰退。然而，GTP与eRF3结合在这些过程中的作用在很大程度上仍不清楚。在这里，我们在酵母中证明了GTP是eRF3与eRF1结合所必需的，但不是与Pab1和UPF1结合所必需的。ERF3的GTP结合基序的突变会削弱eRF1的结合能力，而不会改变Pab1或UPF1的结合活性。有趣的是，该突变不仅导致翻译终止的缺陷，而且延缓了正常和无义介导的mRNA衰退，表明依赖GTP/eRF3的终止对随后的mRNA降解产生了影响。终止反应本身是不够的，但eRF3对于触发mRNA的衰退是必不可少的。因此，eRF3是一个将终止信号转导到mRNA衰变的关键介体。
GTP is essential for eukaryotic translation termination, where the release factor 3 (eRF3) complexed with eRF1 is involved as the guanine nucleotide-binding protein. In addition, eRF3 regulates the termination-coupled events, eRF3 interacts with poly(A)-binding protein (Pab1) and the surveillance factor Upf1 to mediate normal and nonsense-mediated mRNA decay. However, the roles of GTP binding to eRF3 in these processes remain largely unknown. Here, we showed in yeast that GTP is essentially required for the association of eRF3 with eRF1, but not with Pab1 and Upf1. A mutation in the GTP-binding motifs of eRF3 impairs the eRF1-binding ability without altering the Pab1- or Upf1-binding activity. Interestingly, the mutation causes not only a defect in translation termination but also delay of normal and nonsense-mediated mRNA decay, suggesting that GTP/eRF3-dependent termination exerts its influence on the subsequent mRNA degradation. The termination reaction itself is not sufficient, but eRF3 is essential for triggering mRNA decay. Thus, eRF3 is a key mediator that transduces termination signal to mRNA decay.